An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1.
Mutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826277074998919168 |
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| author | Brackenridge, S Evans, E Toebes, M Goonetilleke, N Liu, M di Gleria, K Schumacher, T Davis, S Mcmichael, A Gillespie, G |
| author_facet | Brackenridge, S Evans, E Toebes, M Goonetilleke, N Liu, M di Gleria, K Schumacher, T Davis, S Mcmichael, A Gillespie, G |
| author_sort | Brackenridge, S |
| collection | OXFORD |
| description | Mutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed the appearance of a mutation within the B*57-restricted TW10 epitope (G9E) that did not facilitate strong escape from T cell recognition. The NK cell receptor KIR3DL1, carried by these patients, is known to recognize HLA-B*5703 and is associated with good control of HIV-1. Therefore, we tested whether the G9E mutation influenced the binding of HLA-B*5703 to soluble KIR3DL1 protein by surface plasmon resonance, and while the wild-type sequence and a second (T3N) variant were recognized, the G9E variant abrogated KIR3DL1 binding. We extended the study to determine the peptide sensitivity of KIR3DL1 interaction with epitopes carrying mutations near the C termini of TW10 and a second HLA-B*57-restricted epitope, IW9. Several amino acid changes interfered with KIR3DL1 binding, the most extreme of which included the G9E mutation commonly selected by HLA-B*57. Our results imply that during HIV-1 infection, some early-emerging variants could affect KIR-HLA interaction, with possible implications for immune recognition. |
| first_indexed | 2024-03-06T23:23:26Z |
| format | Journal article |
| id | oxford-uuid:698ea764-4ab9-4c86-9996-d5196b19f9c5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:23:26Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:698ea764-4ab9-4c86-9996-d5196b19f9c52022-03-26T18:51:46ZAn early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:698ea764-4ab9-4c86-9996-d5196b19f9c5EnglishSymplectic Elements at Oxford2011Brackenridge, SEvans, EToebes, MGoonetilleke, NLiu, Mdi Gleria, KSchumacher, TDavis, SMcmichael, AGillespie, GMutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed the appearance of a mutation within the B*57-restricted TW10 epitope (G9E) that did not facilitate strong escape from T cell recognition. The NK cell receptor KIR3DL1, carried by these patients, is known to recognize HLA-B*5703 and is associated with good control of HIV-1. Therefore, we tested whether the G9E mutation influenced the binding of HLA-B*5703 to soluble KIR3DL1 protein by surface plasmon resonance, and while the wild-type sequence and a second (T3N) variant were recognized, the G9E variant abrogated KIR3DL1 binding. We extended the study to determine the peptide sensitivity of KIR3DL1 interaction with epitopes carrying mutations near the C termini of TW10 and a second HLA-B*57-restricted epitope, IW9. Several amino acid changes interfered with KIR3DL1 binding, the most extreme of which included the G9E mutation commonly selected by HLA-B*57. Our results imply that during HIV-1 infection, some early-emerging variants could affect KIR-HLA interaction, with possible implications for immune recognition. |
| spellingShingle | Brackenridge, S Evans, E Toebes, M Goonetilleke, N Liu, M di Gleria, K Schumacher, T Davis, S Mcmichael, A Gillespie, G An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1. |
| title | An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1. |
| title_full | An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1. |
| title_fullStr | An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1. |
| title_full_unstemmed | An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1. |
| title_short | An early HIV mutation within an HLA-B*57-restricted T cell epitope abrogates binding to the killer inhibitory receptor 3DL1. |
| title_sort | early hiv mutation within an hla b 57 restricted t cell epitope abrogates binding to the killer inhibitory receptor 3dl1 |
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